Characterization of the detergent insolubility of the T cell receptor for antigen.
Aggregation of cell surface receptors plays an important role in signal transduction in many receptor systems. In the T cell receptor (TCR), as in many other cell surface receptors, this aggregation results in insolubility in certain nonionic detergents. We have characterized this insolubility for TCR, and we show it is not preexisting in HPB-ALL cells but increases with increasing TCR aggregation. It is not likely to be due to a direct interaction with cellular cytoskeletal elements, as it is not affected by inhibitors of actin or tubulin polymerization. It may be due to interaction with detergent-resistant membrane domains that have been found in various cell types and contain tyrosine kinases, the earliest known participants in TCR signal transduction. This aggregation-dependent insolubility occurs as rapidly as the anti-TCR antibody binds, so the kinetics are consistent with an involvement in signal transduction. It is not, however, dependent on signal transduction, as inhibitors of tyrosine kinases do not inhibit the insolubility. Insolubility is also enhanced by preaggregation of CD4, an important T cell surface molecule which also associates with the tyrosine kinase p56lck.
Marano
N
N
Department of Chemistry, Saint Lawrence University, Canton, NY 13617, USA. nmar@music.stlawu.edu
Crawford
M
M
Govindan
B
B
D015704:CD4 Antigens / Q000737:chemistry / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000737:chemistry / Q000187:drug effects; D016853:Muromonab-CD3 / Q000494:pharmacology; D017830:Octoxynol / Q000494:pharmacology; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011108:Polymers; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism
D015704:CD4 Antigens; D003902:Detergents; D007166:Immunosuppressive Agents; D007527:Isoenzymes; D016853:Muromonab-CD3; D011108:Polymers; D011948:Receptors, Antigen, T-Cell; D017830:Octoxynol; D011505:Protein-Tyrosine Kinases; D017493:Leukocyte Common Antigens; D010738:Type C Phospholipases; D051966:Phospholipase C gamma